Brief Summary of Full Prescribing Information. WARNING

Transcription

Brief Summary of Full Prescribing Information. WARNING
Rx Only
Table 1: Frequencya of Important Treatment Emergent Adverse Events
in the Randomized Study on an Every-3-Weeks Schedule
(Continued)
Percent of Patients
ABRAXANE
Paclitaxel Injection
260/30minb
175/3hc,d
(n=229)
(n=225)
Brief Summary of Full Prescribing Information.
WARNING
ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable
suspension) should be administered under the supervision of a physician experienced in
the use of cancer chemotherapeutic agents. Appropriate management of complications
is possible only when adequate diagnostic and treatment facilities are readily available.
ABRAXANE therapy should not be administered to patients with metastatic breast
cancer who have baseline neutrophil counts of less than 1,500 cells/mm3. In order to
monitor the occurrence of bone marrow suppression, primarily neutropenia, which
may be severe and result in infection, it is recommended that frequent peripheral blood
cell counts be performed on all patients receiving ABRAXANE.
Note: An albumin form of paclitaxel may substantially affect a drug’s functional
properties relative to those of drug in solution. DO NOT SUBSTITUTE FOR OR WITH OTHER
PACLITAXEL FORMULATIONS.
INDICATION:
ABRAXANETM for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is
indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease
or relapse within 6 months of adjuvant chemotherapy. Prior therapy should have included an anthracycline
unless clinically contraindicated.
CONTRAINDICATIONS:
ABRAXANE should not be used in patients who have baseline neutrophil counts of <1,500 cells/mm3.
WARNINGS:
Bone marrow suppression (primarily neutropenia) is dose dependent and a dose limiting toxicity. ABRAXANE
should not be administered to patients with baseline neutrophil counts of <1,500 cells/mm3. Frequent
monitoring of blood counts should be instituted during ABRAXANE treatment. Patients should not be retreated
with subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets
recover to a level >100,000 cells/mm3.
The use of ABRAXANE has not been studied in patients with hepatic or renal dysfunction. In the
randomized controlled trial, patients were excluded for baseline serum bilirubin >1.5 mg/dL or baseline serum
creatinine >2 mg/dL.
Pregnancy – Teratogenic Effects: Pregnancy Category D
ABRAXANE can cause fetal harm when administered to a pregnant woman. Administration of paclitaxel
protein-bound particles to rats on gestation days 7 to 17 at doses of 6 mg/m2 (approximately 2% of the
daily maximum recommended human dose on a mg/m2 basis) caused embryo- and fetotoxicity, as indicated
by intrauterine mortality, increased resorptions (up to 5-fold), reduced numbers of litters and live fetuses,
reduction in fetal body weight and increase in fetal anomalies. Fetal anomalies included soft tissue and skeletal
malformations, such as eye bulge, folded retina, microphthalmia, and dilation of brain ventricles. A lower
incidence of soft tissue and skeletal malformations were also exhibited at 3 mg/m2 (approximately 1% of the
daily maximum recommended human dose on a mg/m2 basis).
There are no adequate and well-controlled studies in pregnant women using ABRAXANE. If this drug
is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be
apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid
becoming pregnant while receiving treatment with ABRAXANE.
Use in Males
Men should be advised to not father a child while receiving treatment with ABRAXANE (see PRECAUTIONS:
Carcinogenesis, Mutagenesis, Impairment of Fertility for discussion of effects of ABRAXANE
exposure on male fertility and embryonic viability).
Albumin (Human)
ABRAXANE contains albumin (human), a derivative of human blood. Based on effective donor screening
and product manufacturing processes, it carries an extremely remote risk for transmission of viral diseases. A
theoretical risk for transmission of Creutzfeldt-Jakob Disease (CJD) also is considered extremely remote. No
cases of transmission of viral diseases or CJD have ever been identified for albumin.
PRECAUTIONS:
Drug Interactions
No drug interaction studies have been conducted with ABRAXANE.
The metabolism of paclitaxel is catalyzed by CYP2C8 and CYP3A4. In the absence of formal clinical
drug interaction studies, caution should be exercised when administering ABRAXANE (paclitaxel protein-bound
particles for injectable suspension) concomitantly with known substrates or inhibitors of CYP2C8 and CYP3A4
(see CLINICAL PHARMACOLOGY).
Potential interactions between paclitaxel, a substrate of CYP3A4, and protease inhibitors (such as
ritonavir, saquinavir, indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been
evaluated in clinical trials.
Hematology
ABRAXANE therapy should not be administered to patients with baseline neutrophil counts of less than 1,500
cells/mm3. In order to monitor the occurrence of myelotoxicity, it is recommended that frequent peripheral
blood cell counts be performed on all patients receiving ABRAXANE. Patients should not be retreated with
subsequent cycles of ABRAXANE until neutrophils recover to a level >1,500 cells/mm3 and platelets recover
to a level >100,000 cells/mm3. In the case of severe neutropenia (<500 cells/mm3 for seven days or more)
during a course of ABRAXANE therapy, a dose reduction for subsequent courses of therapy is recommended
(see DOSAGE AND ADMINISTRATION).
Nervous System
Sensory neuropathy occurs frequently with ABRAXANE. The occurrence of grade 1 or 2 sensory neuropathy
does not generally require dose modification. If grade 3 sensory neuropathy develops, treatment should be
withheld until resolution to grade 1 or 2 followed by a dose reduction for all subsequent courses of ABRAXANE
(see DOSAGE AND ADMINISTRATION).
Injection Site Reaction
Injection site reactions occur infrequently with ABRAXANE and were mild in the randomized clinical trial.
Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible infiltration
during drug administration.
Carcinogenesis, Mutagenesis, Impairment of Fertility
The carcinogenic potential of ABRAXANE has not been studied.
Paclitaxel has been shown to be clastogenic in vitro (chromosome aberrations in human lymphocytes)
and in vivo (micronucleus test in mice). ABRAXANE was not mutagenic in the Ames test or the CHO/HGPRT
gene mutation assay.
Administration of paclitaxel protein-bound particles to male rats at 42 mg/m2 on a weekly basis
(approximately 16% of the daily maximum recommended human exposure on a mg/m2 basis) for 11 weeks
prior to mating with untreated female rats resulted in significantly reduced fertility accompanied by decreased
pregnancy rates and increased loss of embryos in mated females. A low incidence of skeletal and soft tissue
fetal anomalies was also observed at doses of 3 and 12 mg/m2/week in this study (approximately 1% to 5%
of the daily maximum recommended human exposure on a mg/m2 basis). Testicular atrophy/degeneration has
also been observed in single-dose toxicology studies in rodents administered paclitaxel protein-bound particles
at 54 mg/m2 and dogs administered 175 mg/m2 (see WARNINGS).
Pregnancy – Teratogenic Effects: Pregnancy Category D
(See WARNINGS section).
Nursing Mothers
It is not known whether paclitaxel is excreted in human milk. Following intravenous administration of carbon-14
labeled paclitaxel to rats on days 9 to 10 postpartum, concentrations of radioactivity in milk were higher than
in plasma and declined in parallel with the plasma concentrations. Because many drugs are excreted in human
milk and because of the potential for serious adverse reactions in nursing infants, it is recommended that
nursing be discontinued when receiving ABRAXANE therapy.
Pediatric Use
The safety and effectiveness of ABRAXANE in pediatric patients have not been evaluated.
Geriatric Use
Of the 229 patients in the randomized study who received ABRAXANE, 11% were at least 65 years of age
and <2% were 75 years or older. No toxicities occurred notably more frequently among elderly patients
who received ABRAXANE.
ADVERSE REACTIONS:
The following table shows the frequency of important adverse events in the randomized comparative trial
for the patients who received either single-agent ABRAXANE or paclitaxel injection for the treatment of
metastatic breast cancer.
Table 1: Frequencya of Important Treatment Emergent Adverse Events
in the Randomized Study on an Every-3-Weeks Schedule
Percent of Patients
ABRAXANE
Paclitaxel Injection
260/30minb
175/3hc,d
(n=229)
(n=225)
Bone Marrow
Neutropenia
< 2.0 x 109/L
< 0.5 x 109/L
Thrombocytopenia
< 100 x 109/L
< 50 x 109/L
Anemia
< 11 g/L
< 8 g/L
Infections
Febrile Neutropenia
Bleeding
80
9
82
22
2
<1
3
1
33
1
24
2
2
25
<1
20
1
2
Hypersensitivity Reactione
All
4
12
Severef
0
2
Cardiovascular
Vital Sign Changesg
Bradycardia
<1
<1
Hypotension
5
5
Severe Cardiovascular Eventsf
3
4
Abnormal ECG
All patients
60
52
Patients with Normal Baseline
35
30
Respiratory
Cough
6
6
Dyspnea
12
9
Sensory Neuropathy
Any Symptoms
71
56
Severe Symptomsf
10
2
Myalgia/Arthralgia
Any Symptoms
44
49
Severe Symptomsf
8
4
Asthenia
Any Symptoms
47
38
Severe Symptomsf
8
3
Fluid Retention/Edema
Any Symptoms
10
8
Severe Symptomsf
0
1
Gastrointestinal
Nausea
Any symptoms
30
21
Severe symptomsf
3
<1
Vomiting
Any symptoms
18
9
Severe Symptomsf
4
1
Diarrhea
Any Symptoms
26
15
Severe Symptomsf
<1
1
Mucositis
Any Symptoms
7
7
Severe Symptomsf
<1
0
Alopecia
90
94
Hepatic
(Patients with Normal Baseline)
Bilirubin Elevations
7
7
Alkaline Phosphatase Elevations
36
31
AST (SGOT) Elevations
39
32
Injection Site Reaction
1
1
a
Based on worst grade
b
ABRAXANE dose in mg/m2/duration in minutes
c
paclitaxel injection dose in mg/m2/duration in hours
d
paclitaxel injection pts received premedication
e
Includes treatment-related events related to hypersensitivity (e.g., flushing, dyspnea,
chest pain, hypotension) that began on a day of dosing.
f
Severe events are defined as at least grade 3 toxicity
g
During study drug dosing.
Myelosuppression and sensory neuropathy were dose related.
Adverse Event Experiences by Body System
Unless otherwise noted, the following discussion refers to the primary safety database of 229 patients with
metastatic breast cancer treated with single-agent ABRAXANE in the randomized controlled trial. The frequency
and severity of important adverse events for the study are presented above in tabular form. In some instances,
rare severe events observed with paclitaxel injection may be expected to occur with ABRAXANE.
Hematologic
Neutropenia, the most important hematologic toxicity, was dose dependent and reversible. Among patients
with metastatic breast cancer in the randomized trial, neutrophil counts declined below 500 cells/mm3 (Grade
4) in 9% of the patients treated with a dose of 260 mg/m2 compared to 22% in patients receiving paclitaxel
injection at a dose of 175 mg/m2.
In the randomized metastatic breast cancer study, infectious episodes were reported in 24% of the
patients treated with a dose of 260 mg/m2 given as a 30-minute infusion. Oral candidiasis, respiratory tract
infections and pneumonia were the most frequently reported infectious complications. Febrile neutropenia was
reported in 2% of patients in the ABRAXANE arm and 1% of patients in the paclitaxel injection arm.
Thrombocytopenia was uncommon. In the randomized metastatic breast cancer study, bleeding episodes
were reported in 2% of the patients in each treatment arm.
Anemia (Hb <11 g/dL) was observed in 33% of patients treated with ABRAXANE in the randomized trial
and was severe (Hb <8 g/dL) in 1% of the cases. Among all patients with normal baseline hemoglobin, 31%
became anemic on study and 1% had severe anemia.
Hypersensitivity Reactions (HSRs)
In the randomized controlled metastatic breast cancer study, Grade 1 or 2 HSRs occurred on the day of
ABRAXANE administration and consisted of dyspnea (1%) and flushing, hypotension, chest pain, and arrhythmia
(all <1%). The use of ABRAXANE in patients previously exhibiting hypersensitivity to paclitaxel injection or
human albumin has not been studied.
Renal
Overall 11% of patients experienced creatinine elevation, 1% severe. No discontinuations, dose reductions, or
dose delays were caused by renal toxicities.
Gastrointestinal (GI)
Nausea/vomiting, diarrhea, and mucositis were reported by 33%, 27%, and 7% of ABRAXANE treated
patients in the randomized trial.
Rare reports of intestinal obstruction, intestinal perforation, pancreatitis, and ischemic colitis have been
received as part of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE
treatment. Rare reports of neutropenic enterocolitis (typhlitis), despite the coadministration of G-CSF, were
observed in patients treated with paclitaxel injection alone and in combination with other chemotherapeutic
agents.
Injection Site Reaction
Injection site reactions have occurred infrequently with ABRAXANE and were mild in the randomized clinical
trial. Recurrence of skin reactions at a site of previous extravasation following administration of paclitaxel
injection at a different site, i.e., “recall”, has been reported rarely.
Rare reports of more severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and
fibrosis have been received as part of the continuing surveillance of paclitaxel injection safety. In some cases
the onset of the injection site reaction in paclitaxel injection patients either occurred during a prolonged infusion
or was delayed by a week to ten days.
Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible
infiltration during drug administration.
Asthenia
Asthenia was reported in 47% of patients (8% severe) treated with ABRAXANE in the randomized trial. Asthenia
included reports of asthenia, fatigue, weakness, lethargy and malaise.
Other Clinical Events
Rare cases of cardiac ischemia/infarction and thrombosis/embolism possibly related to ABRAXANE treatment
have been reported. Alopecia was observed in almost all of the patients. Nail changes (changes in pigmentation
or discoloration of nail bed) were uncommon. Edema (fluid retention) was infrequent (10% of randomized trial
patients); no patients had severe edema.
The following rare adverse events have been reported as part of the continuing surveillance of paclitaxel
injection safety and may occur following ABRAXANE treatment: skin abnormalities related to radiation recall as
well as reports of maculopapular rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, conjunctivitis,
and increased lacrimation.
Accidental Exposure
No reports of accidental exposure to ABRAXANE have been received. However, upon inhalation of paclitaxel,
dyspnea, chest pain, burning eyes, sore throat, and nausea have been reported. Following topical exposure,
events have included tingling, burning, and redness.
OVERDOSAGE:
There is no known antidote for ABRAXANE overdosage. The primary anticipated complications of overdosage
would consist of bone marrow suppression, sensory neurotoxicity, and mucositis.
DOSAGE AND ADMINISTRATION:
After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of
adjuvant chemotherapy, the recommended regimen for ABRAXANE for Injectable Suspension (paclitaxel
protein-bound particles for injectable suspension) is 260 mg/m2 administered intravenously over 30 minutes
every 3 weeks.
Hepatic Impairment
The appropriate dose of ABRAXANE for patients with bilirubin greater than 1.5 mg/dL is not known.
Dose Reduction
Patients who experience severe neutropenia (neutrophil <500 cells/mm3 for a week or longer) or severe
sensory neuropathy during ABRAXANE therapy should have dosage reduced to 220 mg/m2 for subsequent
courses of ABRAXANE. For recurrence of severe neutropenia or severe sensory neuropathy, additional dose
reduction should be made to 180 mg/m2. For grade 3 sensory neuropathy hold treatment until resolution to
grade 1 or 2, followed by a dose reduction for all subsequent courses of ABRAXANE.
Preparation and Administration Precautions
ABRAXANE is a cytotoxic anticancer drug and, as with other potentially toxic paclitaxel compounds, caution
should be exercised in handling ABRAXANE. The use of gloves is recommended. If ABRAXANE (lyophilized
cake or reconstituted suspension) contacts the skin, wash the skin immediately and thoroughly with soap and
water. Following topical exposure to paclitaxel, events may include tingling, burning and redness. If ABRAXANE
contacts mucous membranes, the membranes should be flushed thoroughly with water.
Given the possibility of extravasation, it is advisable to closely monitor the infusion site for possible
infiltration during drug administration. Limiting the infusion of ABRAXANE to 30 minutes, as directed, reduces
the likelihood of infusion-related reactions (see PRECAUTIONS: Injection Site Reaction).
No premedication to prevent hypersensitivity reactions is required prior to administration of ABRAXANE.
Preparation for Intravenous Administration
ABRAXANE is supplied as a sterile lyophilized powder for reconstitution before use. AVOID ERRORS, READ
ENTIRE PREPARATION INSTRUCTIONS PRIOR TO RECONSTITUTION.
1. Aseptically, reconstitute each vial by injecting 20 mL of 0.9% Sodium
Chloride Injection, USP.
2. Slowly inject the 20 mL of 0.9% Sodium Chloride Injection, USP, over a
minimum of 1 minute, using the sterile syringe to direct the solution flow onto
the INSIDE WALL OF THE VIAL.
3. DO NOT INJECT the 0.9% Sodium Chloride Injection, USP, directly onto the
lyophilized cake as this will result in foaming.
4. Once the injection is complete, allow the vial to sit for a minimum of 5 minutes to ensure proper wetting
of the lyophilized cake/powder.
5. Gently swirl and/or invert the vial slowly for at least 2 minutes until complete dissolution of any cake/
powder occurs. Avoid generation of foam.
6. If foaming or clumping occurs, stand solution for at least 15 minutes until foam subsides.
Each mL of the reconstituted formulation will contain 5 mg/mL paclitaxel.
Calculate the exact total dosing volume of 5 mg/mL suspension required for the patient: Dosing volume
(mL) = Total dose (mg)/5 (mg/mL).
The reconstituted sample should be milky and homogenous without visible particulates. If particulates or
settling are visible, the vial should be gently inverted again to ensure complete resuspension prior to use.
Inject the appropriate amount of reconstituted ABRAXANE into an empty, sterile, polyvinyl chloride (PVC)
type IV bag. The use of specialized DEHP-free solution containers or administration sets is not necessary to
prepare or administer ABRAXANE infusions. The use of an in-line filter is not recommended.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to
administration whenever solution and container permit.
Cardiovascular
Hypotension, during the 30-minute infusion, occurred in 5% of patients in the randomized metastatic breast
cancer trial. Bradycardia, during the 30-minute infusion, occurred in <1% of patients. These vital sign changes
most often caused no symptoms and required neither specific therapy nor treatment discontinuation.
Severe cardiovascular events possibly related to single-agent ABRAXANE occurred in approximately 3%
of patients in the randomized trial. These events included chest pain, cardiac arrest, supraventricular tachycardia,
edema,thrombosis, pulmonary thromboembolism, pulmonary emboli, and hypertension. Cases of cerebrovascular
attacks (strokes) and transient ischemic attacks have been reported rarely.
Electrocardiogram (ECG) abnormalities were common among patients at baseline. ECG abnormalities
on study did not usually result in symptoms, were not dose-limiting, and required no intervention. ECG
abnormalities were noted in 60% of patients in the metastatic breast cancer randomized trial. Among patients
with a normal ECG prior to study entry, 35% of all patients developed an abnormal tracing while on study. The
most frequently reported ECG modifications were non-specific repolarization abnormalities, sinus bradycardia,
and sinus tachycardia.
Stability
Unopened vials of ABRAXANE are stable until the date indicated on the package when stored between
20°C to 25°C (68°F to 77°F), in the original package. Reconstituted ABRAXANE should be used
immediately, but may be refrigerated at 2°C to 8°C (36°F to 46°F) for a maximum of 8 hours if
necessary. If not used immediately, each vial of reconstituted suspension should be replaced in the
original carton to protect it from bright light. Discard any unused portion. Neither freezing nor refrigeration
adversely affects the stability of the product. Some settling of the reconstituted suspension may occur.
Ensure complete resuspension by mild agitation before use. Discard the reconstituted suspension
if precipitates are observed. The suspension for infusion prepared as recommended in an infusion
bag is stable at ambient temperature (approximately 25°C) and lighting conditions for up to 8 hours.
Respiratory
Reports of dyspnea (12%) and cough (6%) were reported after treatment with ABRAXANE in the randomized
trial. Rare reports (<1%) of pneumothorax were reported after treatment with ABRAXANE. Rare reports of
interstitial pneumonia, lung fibrosis, and pulmonary embolism have been received as part of the continuing
surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment. Rare reports of
radiation pneumonitis have been received in paclitaxel injection patients receiving concurrent radiotherapy.
There is no experience with the use of ABRAXANE with concurrent radiotherapy.
Storage
Store the vials in original cartons at 20°C to 25°C (68°F to 77°F). Retain in the original package to protect
from bright light.
Neurologic
The frequency and severity of neurologic manifestations were influenced by prior and/or concomitant
therapy with neurotoxic agents.
In general, the frequency and severity of neurologic manifestations were dose-dependent in patients
receiving single-agent ABRAXANE. In the randomized trial, sensory neuropathy was observed in 71% of
patients (10% severe) in the ABRAXANE arm and in 56% of patients (2% severe) in the paclitaxel injection
arm. The frequency of sensory neuropathy increased with cumulative dose. Sensory neuropathy was the cause
of ABRAXANE discontinuation in 7/229 (3%) patients in the randomized trial. In the randomized comparative
study, 24 patients (10%) treated with ABRAXANE developed Grade 3 peripheral neuropathy; of these patients,
14 had documented improvement after a median of 22 days; 10 patients resumed treatment at a reduced
dose of ABRAXANE and 2 discontinued due to peripheral neuropathy. Of the 10 patients without documented
improvement, 4 discontinued the study due to peripheral neuropathy.
No incidences of grade 4 sensory neuropathies were reported in the clinical trial. Only one incident of
motor neuropathy (grade 1) was observed in either arm of the controlled trial.
Reports of autonomic neuropathy resulting in paralytic ileus have been received as part of the continuing
surveillance of paclitaxel injection safety.
Ocular/visual disturbances occurred in 13% of all patients (n=366) treated with ABRAXANE in single
arm and randomized trials and 1% were severe. The severe cases (keratitis and blurred vision) were reported
in patients in a single arm study who received higher doses than those recommended (300 or 375 mg/m2).
These effects generally have been reversible. However, rare reports in the literature of abnormal visual evoked
potentials in patients treated with paclitaxel injection have suggested persistent optic nerve damage.
Arthralgia/Myalgia
Forty-four percent of patients treated in the randomized trial experienced arthralgia/myalgia; 8% experienced
severe symptoms. The symptoms were usually transient, occurred two or three days after ABRAXANE
administration, and resolved within a few days.
(Continued)
Rare reports of hepatic necrosis and hepatic encephalopathy leading to death have been received as part
of the continuing surveillance of paclitaxel injection safety and may occur following ABRAXANE treatment.
Hepatic
Among patients with normal baseline liver function treated with ABRAXANE in the randomized trial, 7%, 36%,
and 39% had elevations in bilirubin, alkaline phosphatase, and AST (SGOT), respectively. Grade 3 or 4 elevations
in GGT were reported for 14% of patients treated with ABRAXANE and 10% of patients treated with paclitaxel
injection in the randomized trial.
HOW SUPPLIED:
Product
NDC
No.
No.
103450
68817-134-50
100 mg in a single use vial, individually packaged in a carton.
Handling and Disposal
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on
this subject have been published.1-8 There is no general agreement that all of the procedures recommended in
the guidelines are necessary or appropriate.
U.S. Patent Numbers: 5,439,686; 5,498,421; 5,560,933; 5,665,382; 6,096,331; 6,506,405;
6,537,579; 6,749,868; 6,753,006
REFERENCES:
1. Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. Publication No. 83-2621. For
sale by the Superintendent of Documents, US Government NIH Printing Office, Washington, DC 20402.
2. AMA Council Report. Guidelines for Handling Parenteral Antineoplastics. JAMA, 1985; 253(11):15901592.
3. National Study Commission on Cytotoxic Exposure Recommendations for Handling Cytotoxic Agents.
Available from Louis R Jeffrey, ScD, Chairman, National Study Commission on Cytotoxic Exposure.
Massachusetts College of Pharmacy and Allied Health Sciences. 179 Longwood Avenue, Boston,
Massachusetts 02115.
4. Clinical Oncological Society of Australia. Guidelines and Recommendations for Safe Handling of
Antineoplastic Agents. Med J Australia, 1983; 1:426-428.
5. Jones RB, et al: Safe Handling of Chemotherapeutic Agents: A Report from the Mount Sinai Medical Center.
CA-A Cancer Journal for Clinicians, 1983; (Sept/Oct) 258-263.
6. American Society of Hospital Pharmacists Technical Assistance Bulletin on Handling Cytotoxic and Hazardous
Drugs. Am J Hosp Pharm, 1990; 47:1033-1049.
7. Controlling Occupational Exposure to Hazardous Drugs. (OSHA WORK-PRACTICE GUIDELINES.) Am J
Health-Syst Pharm, 1996; 53:1669-1686.
8. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines and Recommendations for Practice.
Pittsburgh,Pa: Oncology Nursing Society; 1999:32-41.
A Division of American Pharmaceutical Partners, Inc.
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